This proposal seeks support to allow the applicant protected time for patient oriented research in metabolic bone disease and to mentor beginning clinicians in early phases of their career in clinical research. The research and mentoring programs are centered around three projects. Project 1 employs family studies to apply the positional cloning approach to identify the gene responsible for autosomal dominant hypophosphatemic rickets. Project 2 also entails studying large kindreds to identify the gene responsible for type 2 autosomal dominant osteopetrosis. This project also studies whether obligate carriers have mild, clinically detectable alterations in osteoclast function. Project 3 is a sibling pair study which uses nonparametric linkage analysis to identify regions of the genome that predispose to low peak bone mass, a necessary prerequisite to identifying these genes. All of the proposed investigations involve human subjects and the projects provide an excellent opportunity to mentor beginning clinicians. Additionally, the PI has extensive experience and success in the study of kindreds with various forms of metabolic bone disease.